PROJECT SUMMARY ? IMMUNOLOGY, MICROENVIRONMENT AND METASTASIS The Immunology, Microenvironment and Metastasis (IMM) Program was launched in 2017 to respond to two strategic needs in the Cancer Center: (i) create an interdisciplinary but cohesive hub for basic and translational tumor immunology research; and (ii) expand a bench-to-bedside effort focused on the tumor microenvironment as a fundamental disease driver and prime therapeutic target. The resulting IMM Program originated from the merge of the former Tumor Microenvironment and Metastasis (TMM) Program in the Cancer Center with the Translational Tumor Immunology (TTI) initiative launched at the Institute in 2015. The ten Cancer Center members that currently comprise the IMM Program have experimental interests that closely align with three main research themes in the biology of the tumor microenvironment: (i) mechanisms of local immunosuppression; (ii) tumor-host crosstalk in disease progression and treatment response; and (iii) pathways of metastatic competence. Despite its relatively recent launch, the IMM Program has critically contributed to all overarching priorities of the Cancer Center, leading successful faculty recruitment in tumor immunology and metastasis, spearheading extensive intra- and inter-programmatic collaborations, promoting broad utilization of Cancer Center Shared Resources, and moving research discoveries to the clinic through successful inter-institutional partnerships. Published in the top-tier literature, contributions from IMM Program members uncovered novel circuitries of immunosuppression by Myeloid-Derived Suppressor Cells (MDSC), characterized new signals of how changes in an aging microenvironment dictate melanoma progression, and defined the contribution of stress-induced mitochondrial reprogramming in metastasis. As a result, the IMM Program currently receives $3 million in NCI funding and a total, cancer-related funding base of $4.7 million, has a rate of collaborative publications of over 40% (intra- and inter-programmatic combined), and 66% of its peer-reviewed, cancer-related funding ($2.3 million) is the product of internal or external collaborations. Currently, the IMM Program contributes to one Specialized Program of Research Excellence (SPORE) in melanoma, three Program Project grants, four multi-PI awards and one U01 grant. Building on these scientific accomplishments, an enveloping culture of transdisciplinary collaboration, and firm commitment to bench-to- bedside cancer research, the IMM Program is ideally poised to fulfill the strategic objectives of the Cancer Center during the next CCSG budget cycle. These will include strengthening an Institute-wide effort in basic and translational immunology synergistically with a reorganized Wistar Vaccine and Immunotherapy Center, expand inter-programmatic contributions in the melanoma research continuum signature, define the interplay between stromal and tumor cells in the emergence of aggressive disease traits, and elucidate mechanisms of metastasis as actionable therapeutic targets.